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Drug Prevents Diabetes and Heart Disease

Posted: Friday, June 22, 2007

An experimental drug prevented mice from developing diabetes and heart disease and might one day be used to stave off the diseases in humans, U.S. researchers said last week. 

The drug, which was developed by researchers at Harvard University in collaboration with Bristol-Meyers Squibb, blocked a protein needed to move fats around the body and made the mice resistant to the diseases. The drug also reversed symptoms of diabetes and heart disease in mice that had them.

"It shoots two big birds with a single bullet," said Gokhan Hotamisligil, chairman of the Harvard School of Public Health's Department of Genetics and Complex Diseases. Mice given the drug became immune to diabetes, heart disease and other metabolic disorders even though they were severely obese or had high cholesterol and extremely high-fat diets.

Hotamisligil's work, published in the journal Nature, builds on his lab's prior discovery of a gene that is linked with diabetes and obesity in mice.

They found that mice who lacked the gene resisted those diseases. "No matter what we did, we couldn't get them to develop diabetes," he said in a interview. "They wouldn't develop heart disease. They couldn't get asthma. They were incredible."
He said the gene controls a lipid-binding protein called aP2 that sticks to fats in the blood and escorts them to different places in the body where they can cause trouble.

When people eat fatty foods, these aP2 proteins trigger a chain of inflammatory responses, he said. They can reduce sensitivity to the sugar-lowering effects of the hormone insulin -- raising the risk of diabetes -- and encourage plaque formation in arteries -- raising the risk of heart attack.

Since the researchers could not genetically modify humans, they needed a chemical to do it for them. "Then comes the question, 'Since we cannot change the genes of people, can we do this trick with a chemical?"' he asked.

Hotamisligil worked with Bristol-Myers Squibb researcher Dr. Rex Parker to make a drug that could block this protein.  They came up with BMS309403, a compound that mimics the act of genetically removing the aP2 gene.

Last year, Harvard researchers found a mutation of the same gene in some humans, who had a reduced risk of diabetes and heart attacks despite consuming a high-fat diet.

"We know this works exactly the same way in humans and we know this compound can do what genetics does. This is very encouraging," he said.

But there's a lot of work ahead for his lab and research partner Bristol-Myers, which jointly owns the compound with Harvard.

For one, they need to prove the chemical isn't toxic in humans. "That issue still needs to be tested. It is not going to be curing everything tomorrow," he said.

But if this or a similar compound proves to be safe and effective in humans, "then we would have a wonderful drug," he said.

Source: Diabetes In Control

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